Nasal devices

ABSTRACT

A nasal delivery device and a method of delivering substance to a nasal airway of a subject can be used for mass treatment, especially mass vaccination. The delivery device can include an interface unit, as a replaceable unit, having at least one nosepiece unit for fitting to a respective nostril of a subject, a nozzle from which substance is in use delivered, and at least one delivery unit having a substance supply unit for delivering substance to the nozzle of the at least one nosepiece unit. The delivery device can also include an actuation unit for actuating the at least one delivery unit of the interface unit.

The present invention relates to a nasal delivery device for and amethod of delivering a substance, in particular one of a liquid, as asuspension or solution, or a powder containing a medicament, especiallysystemic or topical pharmaceuticals, or a vaccine to the nasal airway ofa subject, in particular for the mass treatment, especially vaccination,of subjects.

Referring to FIG. 1, the nasal airway 1 comprises the two nasal cavitiesseparated by the nasal septum, which airway 1 includes numerous ostia,such as the paranasal sinus ostia 3 and the tubal ostia 5, and olfactorycells, and is lined by the nasal mucosa. The nasal airway 1 cancommunicate with the nasopharynx 7, the oral cavity 9 and the lowerairway 11, with the nasal airway 1 being in selective communication withthe anterior region of the nasopharynx 7 and the oral cavity 9 byopening and closing of the oropharyngeal velum 13. The velum 13, whichis often referred to as the soft palate, is illustrated in solid line inthe closed position, as achieved by providing a certain positivepressure in the oral cavity 9, such as achieved on exhalation throughthe oral cavity 9, and in dashed line in the open position.

There are many nasal conditions which require treatment. One suchcondition is nasal inflammation, specifically rhinitis, which can beallergic or non-allergic and is often associated with infection andprevents normal nasal function. By way of example, allergic andnon-allergic inflammation of the nasal airway can typically effectbetween 10 and 20% of the population, with nasal congestion of theerectile tissues of the nasal concha, lacrimation, secretion of waterymucus, sneezing and itching being the most common symptoms. As will beunderstood, nasal congestion impedes nasal breathing and promotes oralbreathing, leading to snoring and sleep disturbance. Other nasalconditions include nasal polyps which arise from the paranasal sinuses,hypertrophic adenoids, secretory otitis media, sinus disease and reducedolfaction.

In the treatment of certain nasal conditions, the topical administrationof medicaments is preferable, particularly where the nasal mucosa is theprime pathological pathway, such as in treating or relieving nasalcongestion. Medicaments that are commonly topically delivered includedecongestants, anti-histamines, cromoglycates, steroids and antibiotics.At present, among the known anti-inflammatory pharmaceuticals, topicalsteroids have been shown to have an effect on nasal congestion. Topicaldecongestants have also been suggested for use in relieving nasalcongestion. The treatment of hypertrophic adenoids and chronic secretoryotitis media using topical decongestants, steroids and anti-microbialagents, although somewhat controversial, has also been proposed.Further, the topical administration of pharmaceuticals has been used totreat or at least relieve symptoms of inflammation in the anteriorregion of the nasopharynx, the paranasal sinuses and the auditory tubes.

Medicaments can also be systemically delivered through the nasalpathway, the nasal pathway offering a good administration route for thesystemic delivery of pharmaceuticals, such as hormones, for example,oxytocin and calcitonin, and analgetics, such as anti-migrainecompositions, as the high blood flow and large surface area of the nasalmucosa advantageously provides for rapid systemic uptake.

Nasal delivery also provides for the administration of medicamentsrequiring a rapid onset of action, for example, analgetics,anti-emetics, insulin, anti-epileptics, sedatives and hypnotica, andalso other pharmaceuticals, for example, cardio-vascular drugs. It isenvisaged that nasal administration will provide for a fast onset ofaction, at a rate similar to that of injection and at a rate much fasterthan that of oral administration. Indeed, for the treatment of manyacute conditions, nasal administration is advantageous over oraladministration, since gastric stasis can further slow the onset ofaction following oral administration.

Nasal delivery also further provides an effective delivery route for theadministration of proteins and peptides as produced by modernbiotechnological techniques. For such substances, the metabolism in theintestines and the first-pass-effect in the liver represent significantobstacles for reliable and cost-efficient delivery.

Furthermore, nasal delivery also further provides for the treatment ofmany common neurological diseases, such as Alzheimer's, Parkinson's,psychiatric diseases and intracerebral infections, where not possibleusing existing techniques. The nasal delivery technique of the presentinvention allows for delivery to the olfactory region, which region islocated in the superior region of the nasal cavities and represents theonly region where it is possible to circumvent the blood-to-brainbarrier (BBB) and enable communication with the cerebrospinal fluid(CSF) and the brain.

Still furthermore, and a prime focus of the present invention is thenasal delivery of vaccines. The nasal delivery device of the presentinvention has been developed with the particular aim of providing adelivery device for the mass treatment, in particular the massvaccination, of subjects.

For any kind of drug delivery, accurate and reliable dosing isessential, but it is of particular importance in relation to theadministration of potent drugs which have a narrow therapeutic window,drugs with potentially serious adverse effects and drugs for thetreatment of serious and life-threatening conditions. For someconditions, it is essential to individualize the dosage to theparticular situation, for example, in the case of diabetes mellitus. Fordiabetes, and, indeed, for many other conditions, the dosage of thepharmaceutical is preferably based on actual real-time measurements.Currently, blood samples are most frequently used, but the analysis ofmolecules in the exhalation breath of subjects has been proposed as analternative to blood analysis for several conditions. Breath analysis iscurrently used for the diagnosis of conditions such as helicobacterpylori infections which cause gastric ulcers.

WO-A-00/51672 discloses a delivery device for delivering a substance, inparticular a medicament, in a bi-directional flow through the nasalcavities, that is, an air flow which passes into one nostril, around theposterior margin of the nasal septum and in the opposite direction outof the other nostril. This bi-directional air flow advantageously actsto stimulate the sensory nerves in the nasal mucosa, therebyconditioning the subject for the delivery and providing a morecomfortable delivery situation.

It is an aim of the present invention to provide improved nasal deliverydevices and nasal delivery methods for providing for the delivery ofsubstance to subjects, in particular for the mass treatment, especiallyvaccination, of subjects.

In one aspect the present invention provides a nasal delivery device fordelivering substance to a nasal airway of a subject, comprising: aninterface unit, as a replaceable unit, including at least one nosepieceunit for fitting to a respective nostril of a subject and including anozzle from which substance is in use delivered, and at least onedelivery unit including a substance supply unit for delivering substanceto the nozzle of the at least one nosepiece unit; and an actuation unitfor actuating the at least one delivery unit of the interface unit.

Preferably, the interface unit comprises a disposable unit.

Preferably, the interface unit comprises a single integral unit.

Preferably, the interface unit is packaged in protective packaging.

In one embodiment the delivery device comprises: a plurality ofinterface units attached to a belt such as to allow for successiveattachment of the interface units to the actuation unit.

Preferably, the actuation unit is configured successively to provide theinterface units thereto through use of the belt as a guide.

Preferably, the substance supply unit comprises a substance pump unitfor delivering substance, the substance pump unit including a chambercontaining substance and a piston member which is movable in the chamberto deliver a flow of substance from the chamber.

In one embodiment the substance comprises a liquid.

In another embodiment the substance comprises a powder.

Preferably, the interface unit includes a mouthpiece unit including amouthpiece into which a subject in use exhales.

In one embodiment the mouthpiece is fluidly connected to the at leastone nosepiece unit such as to provide an air flow therethrough onexhalation by a subject into the mouthpiece.

In one embodiment the at least one delivery unit includes a gas supplyunit for supplying a gas flow through the at least one nosepiece unit.

Preferably, the gas supply unit comprises a gas pump unit for deliveringa gas flow, the gas pump unit comprising a cylinder and a piston memberwhich is movable in the cylinder to deliver a gas flow through the atleast one nosepiece unit.

In one embodiment the at least one delivery unit is configured such thatthe gas supply unit initiates supply of a gas flow prior to actuation ofthe substance supply unit to deliver substance.

In another embodiment the actuation unit includes a gas supply unit forsupplying a gas flow through the at least one nosepiece unit.

In one embodiment the actuation unit is configured such that the gassupply unit initiates supply of a gas flow prior to actuation of thesubstance supply unit to deliver substance.

Preferably, the at least one delivery unit is actuated in response toexhalation by the subject.

In one embodiment the actuation unit includes a detection unit fordetecting exhalation by a subject, at least one drive unit for actuatingthe at least one delivery unit, and a control unit for actuating the atleast one drive unit in response to detecting exhalation by the subject.

In one embodiment the detection unit includes a pressure sensor fordetecting a pressure in the mouthpiece, and the control unit isconfigured to actuate the at least one drive unit in response todetection of a predeterminable pressure by the detection unit.

In another embodiment the detection unit includes a flow sensor fordetecting a flow rate through the mouthpiece, and the control unit isconfigured to actuate the at least one drive unit in response todetection of a predeterminable flow rate by the detection unit.

In another embodiment the actuation unit includes at least one driveunit for actuating the at least one delivery unit, and a triggermechanism for actuating the at least one drive unit in response toexhalation by the subject.

In one embodiment the trigger mechanism is configured to actuate the atleast one drive unit in response to generation of a predeterminablepressure in the mouthpiece.

In another embodiment the trigger mechanism is configured to actuate theat least one drive unit in response to detection of a predeterminableflow rate through the mouthpiece.

Preferably, the interface unit includes first and second nosepiece unitsfor fitting to respective nostrils of the subject, and first and seconddelivery units, each including a substance supply unit for deliveringsubstance through the respective nosepiece unit.

More preferably, the actuation unit is configured to actuate the firstand second delivery units in succession such that substance is firstdelivered into one nasal cavity and subsequently into the other nasalcavity.

In another aspect the present invention provides a method of deliveringsubstance to a nasal airway of a subject, comprising the steps of:providing an interface unit, as a replaceable unit, to an actuationunit, the interface unit including at least one nosepiece unit forfitting to a respective nostril of a subject and including a nozzle fromwhich substance is delivered, and at least one delivery unit including asubstance supply unit for delivering substance to the nozzle of the atleast one nosepiece unit, and the actuation unit being configured toactuate the at least one delivery unit of the interface unit; fittingthe interface unit to a subject; and actuating the actuation unit toactuate the at least one delivery unit such as to deliver substance to anasal airway of the subject.

Preferably, the interface unit comprises a disposable unit.

Preferably, the interface unit comprises a single integral unit.

Preferably, the interface unit is packaged in protective packaging, and,prior to the fitting step, the method further comprises the step of:opening the protective packaging.

In one embodiment a plurality of interface units are attached to a belt,and, in the interface unit providing step, a subsequent one of theinterface units is provided to the actuation unit.

Preferably, in the interface unit providing step, the actuation unitadvances the belt of interface units such as to provide a subsequent oneof the interface units thereto.

Preferably, the substance supply unit comprises a substance pump unitfor delivering substance, and the substance pump unit includes a chambercontaining substance and a piston member which is moved in the chamberto deliver a flow of substance from the chamber.

In one embodiment the substance comprises a liquid.

In another embodiment the substance comprises a powder.

Preferably, the interface unit includes a mouthpiece unit including amouthpiece, and, prior to the actuation unit actuating step, the methodfurther comprises the step of: the subject exhaling into the mouthpiece.

In one embodiment the mouthpiece is fluidly connected to the at leastone nosepiece unit such as to provide an air flow therethrough onexhalation by the subject into the mouthpiece.

In one embodiment the at least one delivery unit includes a gas supplyunit for supplying a gas flow, and the method further comprises the stepof: actuating the gas supply unit to supply a gas flow through the atleast one nosepiece unit.

Preferably, the gas supply unit comprises a gas pump unit for deliveringa gas flow, and the gas pump unit comprises a cylinder and a pistonmember which is moved in the cylinder to deliver a gas flow through theat least one nosepiece unit.

In one embodiment, for each delivery unit, the supply of a gas flow isinitiated prior to the delivery of substance.

In another embodiment the actuation unit includes a gas supply unit forsupplying a gas flow, and the method further comprises the step of:actuating the gas supply unit to supply a gas flow through the at leastone nosepiece unit.

In one embodiment, for each delivery unit, the supply of a gas flow isinitiated prior to the delivery of substance.

Preferably, the at least one delivery unit is actuated in response toexhalation by the subject.

In one embodiment the actuation unit includes a detection unit fordetecting exhalation by the subject and at least one drive unit foractuating the at least one delivery unit; and the actuation unitactuating step comprises the step of: actuating the at least one driveunit in response to the detection unit detecting exhalation by thesubject.

In one embodiment the detection unit includes a pressure sensor fordetecting a pressure in the mouthpiece, and the at least one drive unitis actuated in response to detection of a predeterminable pressure bythe detection unit.

In another embodiment the detection unit includes a flow sensor fordetecting a flow rate through the mouthpiece, and the at least one driveunit is actuated in response to detection of a predeterminable flow rateby the detection unit.

In another embodiment the actuation unit includes at least one driveunit for actuating the at least one delivery unit and a triggermechanism for actuating the at least one drive unit in response toexhalation by the subject; and the actuation unit actuating stepcomprises the step of: actuating the trigger mechanism to actuate the atleast one drive unit in response to exhalation by the subject.

In one embodiment the trigger mechanism is configured to actuate the atleast one drive unit in response to generation of a predeterminablepressure in the mouthpiece.

In another embodiment the trigger mechanism is configured to actuate theat least one drive unit in response to detection of a predeterminableflow rate through the mouthpiece.

Preferably, the interface unit includes first and second nosepiece unitsfor fitting to respective nostrils of the subject, and first and seconddelivery units, each including a substance supply unit for deliveringsubstance through the respective nosepiece unit, and the actuation unitactuating step comprises the step of: actuating the actuation unit toactuate the first and second delivery units such as to deliver substanceto the respective nasal cavities of the subject.

In one embodiment the first and second delivery units are actuated insuccession such that substance is first delivered into one nasal cavityand subsequently into the other nasal cavity.

Preferably, the method is for the mass treatment of subjects, inparticular the mass vaccination of subjects.

In a further aspect the present invention provides a nasal deliverycomponent, as a disposable component, comprising at least one nosepieceunit for fitting to a respective nostril of a subject and including anozzle from which substance is in use delivered, and at least onedelivery unit including a substance supply unit for delivering substanceto the nozzle of the at least one nosepiece unit.

Preferably, the delivery component is an interface unit for attachmentto an actuation unit utilized in actuating the at least one deliveryunit.

In one embodiment a plurality of delivery units are attached to a beltsuch as to allow for successive attachment to the actuation unit.

Preferably, the at least one delivery unit is manually actuatable absentan actuation unit.

Preferably, the delivery component is packaged in protective packaging.

Preferably, the substance supply unit comprises a substance pump unitfor delivering substance, the substance pump unit including a chambercontaining substance and a piston member which is movable in the chamberto deliver a flow of substance from the chamber.

In one embodiment the substance is a liquid.

In another embodiment the substance is a powder.

Preferably, the delivery component further comprises a mouthpiece unitincluding a mouthpiece into which the subject in use exhales.

In one embodiment the mouthpiece is fluidly connected to the at leastone nosepiece unit such as to provide an air flow therethrough onexhalation by the subject into the mouthpiece.

In one embodiment the at least one delivery unit includes a gas supplyunit for supplying a gas flow through the at least one nosepiece unit.

Preferably, the gas supply unit comprises a gas pump unit for deliveringa gas flow, the gas pump unit including a cylinder and a piston memberwhich is movable in the cylinder to deliver a gas flow through therespective nosepiece unit.

In one embodiment the at least one delivery unit is configured such thatthe gas supply unit initiates supply of a gas flow prior to thesubstance supply unit delivering substance.

Preferably, the delivery unit comprises first and second nosepiece unitsfor fitting to respective nostrils of the subject, and first and seconddelivery units, each for delivering substance through a respective oneof the first and second nosepiece units.

Preferably, the delivery component is configured such as to be separablebetween the first and second nosepiece units, and thereby provide twodelivery units which are each separably operable.

In a yet further aspect the present invention provides an actuation unitfor receiving and actuating an interface unit, as a replaceable unit, todeliver substance to a nasal airway of a subject, the interface unitincluding at least one nosepiece unit for fitting to a respectivenostril of a subject and including a nozzle from which substance is inuse delivered, and at least one delivery unit including a substancesupply unit for delivering substance to the nozzle of the at least onenosepiece unit, the actuation unit comprising: at least one drive unitfor actuating the at least one delivery unit of the interface unit.

Preferably, the interface unit includes a mouthpiece unit including amouthpiece into which the subject in use exhales.

In one embodiment the mouthpiece is fluidly connected to the at leastone nosepiece unit such as to provide an air flow therethrough onexhalation by the subject into the mouthpiece.

In one embodiment the actuation unit further comprises: a detection unitfor detecting exhalation by the subject into the mouthpiece; and acontrol unit for actuating the at least one drive unit in response todetecting exhalation by the subject.

In one embodiment the detection unit includes a pressure sensor fordetecting a pressure in the mouthpiece, and the control unit isconfigured to actuate the at least one drive unit in response todetection of a predeterminable pressure by the detection unit.

In another embodiment the detection unit includes a flow sensor fordetecting a flow rate through the mouthpiece, and the control unit isconfigured to actuate the at least one drive unit in response todetection of a predeterminable flow rate by the detection unit.

In another embodiment the actuation unit further comprises: a triggermechanism for actuating the at least one delivery unit in response toexhalation by the subject into the mouthpiece.

In one embodiment the trigger mechanism is configured to actuate the atleast one drive unit in response to generation of a predeterminablepressure in the mouthpiece.

In another embodiment the trigger mechanism is configured to actuate theat least one drive unit in response to detection of a predeterminableflow rate through the mouthpiece.

In one embodiment the at least one delivery unit includes a gas supplyunit for supplying a gas flow through the at least one nosepiece unit.

In another embodiment the actuation unit further comprises: a gas supplyunit for supplying a gas flow through the at least one nosepiece unit.

In one embodiment a plurality of interface units are attached to a belt,and the actuation unit is configured to advance the belt such assuccessively to provide interface units thereto.

Preferably, the belt to which the interface units are attached isutilized as a guide.

Preferably, the interface unit includes first and second nosepiece unitsfor fitting to respective nostrils of the subject, and first and seconddelivery units, each for delivering substance through respective ones ofthe first and second nosepiece units, and the actuation unit furthercomprises: first and second drive units for actuating respective ones ofthe delivery units of the interface unit.

More preferably, the first and second drive units are configured toactuate the substance supply units in succession, and thereby deliversubstance first into one nasal cavity and subsequently into the othernasal cavity.

Preferred embodiments of the present invention will now be describedhereinbelow by way of example only with reference to the accompanyingdrawings, in which:

FIG. 1 schematically illustrates the anatomy of the upper respiratorytract of a human subject;

FIG. 2 illustrates a nasal delivery device in accordance with a firstembodiment of the present invention;

FIG. 3 illustrates a sectional view through the nosepiece units anddelivery units of the interface unit of the delivery device of FIG. 2;

FIG. 4 illustrates a sectional view through the mouthpiece unit of theinterface unit of the delivery device of FIG. 2;

FIG. 5 schematically represents the actuation unit of the deliverydevice of FIG. 2;

FIGS. 6(a) to (d) illustrate the operation of the delivery device ofFIG. 2;

FIGS. 7(a) and (b) illustrate one modification of the interface unit ofthe delivery device of FIG. 2;

FIG. 8 illustrates an interface unit supply as another modification ofthe delivery device of FIG. 2;

FIG. 9 illustrates a nasal delivery device in accordance with a secondembodiment of the present invention;

FIG. 10 illustrates a sectional view through the nosepiece units anddelivery units of the interface unit and the actuation unit of thedelivery device of FIG. 9;

FIG. 11 illustrates a sectional view through the mouthpiece unit of theinterface unit of the delivery device of FIG. 8; and

FIGS. 12(a) to (e) illustrate the operation of the delivery device ofFIG. 9.

FIGS. 2 to 6 illustrate a nasal delivery device in accordance with afirst embodiment of the present invention.

The delivery device comprises an interface unit 21 for fitting to asubject and containing the substance to be delivered, and an actuationunit 23 to which the interface unit 21 is attached to enable thedelivery of the substance from the interface unit 21 on exhalation bythe subject. In this embodiment the interface unit 21 is a disposablecomponent and the means of attachment of the interface unit 21 to theactuation unit 23 is such as to allow for the easy, repeated attachmentof interface units 21 to allow for the treatment of large numbers ofsubjects, such as in the mass vaccination of subjects.

The interface unit 21 comprises a main body 25 for attachment to theactuation unit 23, in this embodiment as a sliding fit. In analternative embodiment the main body 25 could be configured to be a clipfit to the actuation unit 23. In this embodiment the means of attachmentof the interface unit 21 to the actuation unit 23 is configured, here bythe provision of differently-shaped slide features, such as to providefor the attachment of the interface unit 21 to the actuation unit 23 inthe correct orient.

The interface unit 21 further comprises first and second nosepiece units27, 29 for fitting to respective ones of the nostrils of a subject.

The nosepiece units 27, 29 each comprise a cuff member 31, in thisembodiment a frusto-conical element, for positioning the respectivenosepiece unit 27, 29 in a nasal cavity of the subject and providing afluid-tight seal therewith, and an outlet unit 33 for deliveringsubstance into the respective nasal cavity of the subject.

Each outlet unit 33 comprises a nozzle 35 from which substance isdelivered into the respective nasal cavity of the subject, and adelivery channel 37 through which a gas flow, in this embodimentseparate from the exhalation breath of the subject, is delivered toentrain the substance delivered from the nozzle 35.

In this embodiment the nozzle 35 is configured to provide an aerosolspray. In an alternative embodiment, for the delivery of a liquid, thenozzle 35 could be configured to deliver a liquid jet as a column ofliquid.

In this embodiment the nozzle 35 is disposed in the delivery channel 37co-axially with the same. In this embodiment the delivery channel 37 isan annular channel which surrounds the nozzle 35 such as to define anannular gas flow which entrains the substance delivered from the nozzle35.

The interface unit 21 further comprises first and second delivery units39, 41 which are fluidly connected to respective ones of the first andsecond nosepiece units 27, 29. The delivery units 39, 41 each comprise asubstance supply unit 43 for delivering a metered dose of a substance tothe respective nozzle 35 and a gas supply unit 45 for delivering ametered volume of a gas, in this embodiment separate to the exhalationbreath of the subject, as a gas flow through the respective deliverychannel 37. In preferred embodiments the substance comprises amedicament, especially systemic or topical pharmaceuticals, or avaccine.

In this embodiment each substance supply unit 43 comprises a liquiddelivery pump for delivering a metered dose of a substance on actuationthereof, as one of an aerosol spray or a liquid jet as a column ofliquid from the respective nozzle 35.

Each substance supply unit 43 comprises a piston unit which comprises acylinder 47 which defines a chamber 49 and into one, forward end ofwhich a hollow needle 51 extends as an extension of the respectivenozzle 35.

Each substance supply unit 43 further comprises first and second pistons53, 55 which contain a volume of substance therebetween and are movablydisposed within the chamber 49.

With this configuration, as illustrated in FIGS. 6(b) and (c), theforward piston 53 is driven forwardly on the rear piston 55 being drivenforwardly, the substance contained between the pistons 53, 55 beingsubstantially incompressible. The forward piston 53 is a puncturablemember which is punctured by the needle 51 of the respective nozzle 35on being driven onto the same, with the needle 51 of the respectivenozzle 35 being in fluid communication with the substance containedbetween the pistons 53, 55 on puncturing the forward piston 53.

In this embodiment the forward piston 53 is spaced from the needle 51 ofthe respective nozzle 35 by a predetermined distance such that therespective gas supply unit 45 is actuated to commence delivery of a gasflow through the respective delivery channel 37 at least simultaneouslywith the delivery of substance to the respective nozzle 35, and in apreferred embodiment prior to the delivery of substance to therespective nozzle 35.

In another alternative embodiment each substance supply unit 43 couldcomprise a powder delivery pump for delivering a metered dose of a drypowder on actuation thereof.

In a further alternative embodiment each substance supply unit 43 couldcomprise a dry powder delivery unit which delivers a metered dose of asubstance, as a dry powder, on actuation thereof.

In another alternative embodiment each substance supply unit 43 couldcomprise an aerosol canister for delivering a metered volume of apropellant or the like, containing a substance, either as a suspensionor solution.

Each gas supply unit 45 comprises a cylinder 57, in this embodimentdefined by the main body 25 and being open at the forward end andbounded at the rear end by a rear wall of the main body 25, and a piston59 which is coupled to the rear piston 55 of the respective substancesupply unit 43 and movably disposed within the cylinder 57 between afirst, non-actuated position and a second, actuated position such as todrive a volume of gas, in this embodiment about 5 ml, through therespective delivery channel 37 on actuation thereof. FIGS. 6(b) and 6(c)illustrate the actuation of the gas supply unit 45 of respective ones ofthe first and second delivery units 39, 41.

The cylinder 57 comprises a first, rear section 57 a at which the piston59 is disposed in the non-actuated position, a second, intermediatesection 57 b at which the piston 59 is disposed during actuation of thepiston 59 and a third, forward section 57 c at which the piston 59 isdisposed in the actuated position, a port 61 which fluidly connects therear section 57 a to atmosphere, and a clearance hole 63 at the rear endthereof to allow for the extension of a drive rod 81 of a respectivedrive unit 75, 77 of the actuation unit 23 therethrough in driving therear piston 55 of the respective substance supply unit 43 and the piston59 of the respective gas supply unit 45.

In this embodiment the port 61 is configured to set the flow resistanceof a gas flow driven through the respective nosepiece unit 27, 29. In apreferred embodiment the port 61 is fluidly connected to a filter whichacts to trap any substance driven through the respective nosepiece unit27, 29.

In this embodiment the clearance hole 63 is configured to be a sealingfit with a drive rod 81 of a respective drive unit 75, 77 of theactuation unit 23, but need not be a sealing fit, as there is norequirement for a sealing fit. In an alternative embodiment the rearwall of the main body 25, which defines the rear end of each cylinder57, can comprise a resilient material which is deflected by the driverod 81 of the respective drive unit 75, 77 of the actuation unit 23.

The rear section 57 a of the cylinder 57 has a greater radial dimensionthan the piston 59 such that, when the piston 59 is in the non-actuatedposition, an annular channel is defined about the piston 59 in fluidcommunication with the port 61, whereby a gas flow driven into therespective nosepiece unit 27, 29 from the other nosepiece unit 27, 29 isvented to atmosphere through the port 61. In this embodiment the firstand second delivery units 39, 41 are actuated in succession such thatthe piston 59 of one of the delivery units 39, 41 is in the non-actuatedposition during actuation of the other of the delivery units 39, 41,thereby providing a flow path through the one nosepiece unit 27, 29.

The intermediate section 57 b of the cylinder 57 has the same radialdimension as the piston 59 such that the piston 59 is a sealing fittherein, whereby a gas flow is driven through the respective deliverychannel 37 during displacement of the piston 59 thereover. In thisembodiment the volume of the gas flow is determined by the length of theintermediate section 57 b of the cylinder 57.

The forward section 57 c of the cylinder 57 has a greater radialdimension than the piston 59 such that, when the piston 59 is in theactuated position, an annular channel is defined about the piston 59 influid communication with the port 61, whereby a gas flow driven into therespective nosepiece unit 27, 29 from the other nosepiece unit 27, 29 isvented to atmosphere through the port 61. In this embodiment, where thefirst and second delivery units 39, 41 are actuated in succession, thepiston 59 of the other of the delivery units 39, 41, that is, thedelivery unit 39, 41 which is first actuated, is in the actuatedposition during actuation of the other of the delivery units 39, 41,thereby providing a flow path to atmosphere through the other nosepieceunit 27, 29.

The piston 59 comprises an annular element 65 and a connecting rod 66which is coupled to the rear piston 55 of the respective substancesupply unit 43. The annular element 65 includes a stepped peripheraledge 67, the peripheral edge 67 including a first, forward section 67 ahaving the same radial dimension as the intermediate section 57 b of thecylinder 57 such as to be a sealing fit therewith, and a second, rearsection 67 b having a smaller radial dimension than the forward section67 a such as to provide an annular flow path about the peripheral edge67 when the piston 59 is in the actuated position.

In this embodiment the annular element 65 is configured to sealinglyengage the rear end of the respective cylinder 57, and thereby close therespective clearance hole 63, when in the non-actuated position.

The interface unit 21 further comprises a mouthpiece unit 69 into whichthe subject exhales to actuate the actuation unit 23. In this embodimentthe mouthpiece unit 69 comprises a mouthpiece 71, here configured to begripped in the lips of the subject, and a flexible element 73, here aresilient membrane, which is disposed across the rear end of themouthpiece 71 such as to be acted upon by the exhalation breath of thesubject and be deflected thereby. As will be described in more detailhereinbelow, the actuation unit 23 includes a control unit 89 which isactuated by a predetermined deflection of the flexible element 73, whichdeflection corresponds to the establishment of a predetermined pressurein the oral cavity of the subject sufficient for closure of theoropharyngeal velum.

The actuation unit 23 comprises a housing 74 to which an interface unit21 is attachable for the treatment of a subject, the interface unit 21being a disposable unit, with a fresh interface unit 21 being attachedto the housing 74 for each subject to be treated. In this embodiment, inproviding that all surfaces, which are brought into contact with asubject or contacted by the exhalation breath of a subject, are confinedto the interface unit 21, there is no possibility of cross-contaminationof treated subjects.

The actuation unit 23 further comprises first and second drive units 75,77 for actuating the respective ones of the delivery units 39, 41 of theinterface unit 21 in response to exhalation by the subject into themouthpiece 71.

In this embodiment the drive units 75, 77 each comprise an actuator 79which includes a drive rod 81, the speed and timing of which iscontrollable to enable control of the delivery profile of the deliveredsubstance. In a preferred embodiment the actuator 79 comprises apneumatic actuator.

The actuation unit 23 further comprises a detection unit 83 fordetecting the exhalation of the subject into the mouthpiece 71 such asto cause closure of the oropharyngeal velum of the subject. In thisembodiment the detection unit 83 comprises a pressure sensor 85 fordetecting a pressure developed in the mouthpiece 71, the pressure sensor85 including a sensing element 87 for sensing the deflection of theresilient element 73 of the mouthpiece unit 69 on exhalation by thesubject into the mouthpiece 71. In an alternative embodiment, where themouthpiece 71 is modified to allow for flow therethrough, the detectionunit 83 could comprise a flow sensor for detecting a flow rate developedthrough the mouthpiece 71 on exhalation by the subject into themouthpiece 71.

The actuation unit 23 further comprises a control unit 89 which isoperably connected to the first and second actuation units 75, 77 andthe detection unit 83 such as successively to actuate the delivery units39, 41 of the interface unit 21 on exhalation by the subject into themouthpiece 71 with sufficient force as to maintain the oropharyngealvelum in the closed position. In this embodiment the timing of theactuation of the actuation units 75, 77 and the delivery profile of theactuation units 75, 77 can be controlled by the control unit 89.

In one embodiment the actuation unit 23 can include means forregistering each subject being treated, such as by photograph, orfingerprint or iris recognition. By registering the subjects beingtreated, an accurate treatment record can be maintained.

In a preferred embodiment the actuation unit 23 can include an over-ridefacility to enable the actuation of the actuation units 75, 77irrespective of the development of an exhalation flow by the subjectwhich is sufficient to close the oropharyngeal velum. Althoughbi-directional delivery through the nasal cavities of a subject isdesirable, this over-ride facility can prove useful where subjectcompliance is poor, such as in infants, and the need for exhalation isnot understood.

Operation of the delivery device is illustrated in FIGS. 6(a) to (d),where FIG. 6(a) illustrates the fitting of the nosepiece units 27, 29 tothe respective nostrils of a subject, and, following exhalation by thesubject into the mouthpiece 71 of the mouthpiece unit 69, FIGS. 6(b) and(c) illustrate the successive actuation of the first and second deliveryunits 39, 41, and FIG. 6(d) illustrates the state subsequent todelivery.

FIGS. 7(a) and (b) illustrate an interface unit 21 as one modificationof the above-described first embodiment.

In this embodiment the interface unit 21 includes protective packaging91 which acts to maintain the interface unit 21 sterile prior to use,and can also provide protection for the contained substance, where thesubstance is sensitive to environmental factors, such as moisture andgas uptake, typically oxygen uptake. FIGS. 7(a) and (b) illustrate theinterface unit 21 with the packaging closed and open respectively.

FIG. 8 illustrates an interface unit supply 93 as another modificationof the above-described first embodiment.

In this embodiment, instead of the interface units 21 being providedsingly, the interface units 21 are mounted on a belt 95 such as to allowfor automated or at least semi-, automated attachment of the interfaceunits 21 in turn.

In a preferred embodiment the actuation unit 23 can include an advancemechanism which acts to advance each interface unit 21 in turn to theattachment position, with the interface units 21 being guided along atrack by the belt 95, whereby the operator is not required to attach theinterface units 21, but merely has to perform a supervisory function.

It will be understood that the interface units 21 of the interface unitsupply 93 could include protective packaging 91 as in theabove-described modification.

FIGS. 9 to 12 illustrate a nasal delivery device in accordance with asecond embodiment of the present invention.

The delivery device comprises an interface unit 121 for fitting to asubject and containing the substance to be delivered, and an actuationunit 123 to which the interface unit 121 is attached to enable thedelivery of the substance from the interface unit 121 on exhalation bythe subject. In this embodiment the interface unit 121 and the actuationunit 123 are disposable components, and the actuation unit 123, in beingof simple construction, enables use in regions which cannot be readilyaccessed by medical personnel, for example, in remote regions, regionsof devastation or regions of epidemic.

The interface unit 121 comprises a main body 125 for attachment to theactuation unit 123, in this embodiment as a sliding fit. In analternative embodiment the main body 125 could be configured to be aclip fit to the actuation unit 123. In this embodiment the means ofattachment of the interface unit 121 to the actuation unit 123 isconfigured, here by the provision of differently shaped slide features,such as to provide for the attachment of the interface unit 121 to theactuation unit 123 in the correct orient.

The interface unit 121 further comprises first and second nosepieceunits 127, 129 for fitting to respective ones of the nostrils of asubject.

The nosepiece units 127, 129 each comprise a cuff member 131, in thisembodiment a frusto-conical element, for positioning the respectivenosepiece unit 127, 129 in a nasal cavity of the subject and providing afluid-tight seal therewith, and an outlet unit 133 for deliveringsubstance into the respective nasal cavity of the subject.

Each outlet unit 133 comprises a nozzle 135 from which substance isdelivered into the respective nasal cavity of the subject, and adelivery channel 137 through which a gas flow, in this embodimentseparate from the exhalation breath of the subject, is delivered toentrain the substance delivered from the nozzle 135. In an alternativeembodiment the interface unit 121 could be configured such that theentraining gas flow is from the exhalation breath of the subject.

In this embodiment the nozzle 135 is configured to provide an aerosolspray. In an alternative embodiment, for the delivery of a liquid, thenozzle 135 could be configured to deliver a liquid jet as a column ofliquid.

In this embodiment the nozzle 135 is disposed in the delivery channel137 co-axially with the same. In this embodiment the delivery channel137 is an annular channel which surrounds the nozzle 135 such as todefine an annular gas flow which entrains the substance delivered fromthe nozzle 135.

The interface unit 121 further comprises first and second delivery units139, 141 which are fluidly connected to respective ones of the first andsecond nosepiece units 127, 129. The delivery units 139, 141 eachcomprise a substance supply unit 143 for delivering a metered dose of asubstance to the respective nozzle 135 and a gas supply unit 145 fordelivering a metered volume of a gas, in this embodiment separate to theexhalation breath of the subject, as a gas flow through the respectivedelivery channel 137. In preferred embodiments the substance comprises amedicament, especially systemic or topical pharmaceuticals, or avaccine.

In this embodiment each substance supply unit 143 comprises a liquiddelivery pump for delivering a metered dose of a substance on actuationthereof, as one of an aerosol spray or a liquid jet as a column ofliquid from the respective nozzle 135.

Each substance supply unit 143 comprises a piston unit which comprises acylinder 147 which defines a chamber 149 and into one, forward end ofwhich a hollow needle 151 extends as an extension of the respectivenozzle 135.

Each substance supply unit 143 further comprises first and secondpistons 153, 155 which contain a volume of substance therebetween andare movably disposed within the respective chamber 149.

With this configuration, as illustrated in FIGS. 12(c) and (d), theforward piston 153 is driven forwardly on the rear piston 155 beingdriven forwardly, the substance contained between the pistons 153, 155being substantially incompressible. The forward piston 153 is apuncturable member which is punctured by the needle 151 of therespective nozzle 135 on being driven onto the same, with the needle 151of the respective nozzle 135 being in fluid communication with thesubstance contained between the pistons 153, 155 on puncturing theforward piston 153.

In this embodiment the forward piston 153 is spaced from the needle 151of the respective nozzle 135 by a predetermined distance such that therespective gas supply unit 145 is actuated to commence delivery of a gasflow through the respective delivery channel 137 at least simultaneouslywith the delivery of substance to the respective nozzle 135, and in apreferred embodiment prior to the delivery of substance to therespective nozzle 135.

In another alternative embodiment each substance supply unit 143 couldcomprise a powder delivery pump for delivering a metered dose of a drypowder on actuation thereof.

In a further alternative embodiment each substance supply unit 143 couldcomprise a dry powder delivery unit which delivers a metered dose of asubstance, as a dry powder, on actuation thereof.

In another alternative embodiment each substance supply unit 143 couldcomprise an aerosol canister for delivering a metered volume of apropellant or the like, containing a substance, either as a suspensionor solution.

Each gas supply unit 145 comprises a cylinder 157, in this embodimentdefined by the main body 125 and being open at the forward end andclosed at the rear end by a rear wall of the main body 125, and a piston159 which is coupled to the rear piston 155 of the respective substancesupply unit 143 and movably disposed within the cylinder 157 between afirst, non-actuated position and a second, actuated position such as todrive a volume of gas, in this embodiment about 5 ml, through therespective delivery channel 137 on actuation thereof. FIGS. 12(c) and(d) illustrate the actuation of the gas supply unit 145 of respectiveones of the first and second delivery units 139, 141.

The cylinder 157 comprises a first, rear section 157 a at which thepiston 159 is disposed in the non-actuated position, a second,intermediate section 157 b at which the piston 159 is disposed duringactuation of the piston 159 and a third, forward section 157 c at whichthe piston 159 is disposed in the actuated position, a port 161 whichfluidly connects the rear section 157 a to atmosphere, and a clearancehole 163 at the rear end thereof to allow for the extension of a drivingrod 181 of a respective drive unit 175, 177 of the actuation unit 123therethrough in driving the rear piston 155 of the respective substancesupply unit 143 and the piston 159 of the respective gas supply unit145.

In this embodiment the port 161 is configured to set the flow resistanceof a gas flow driven through the respective nosepiece unit 127, 129. Ina preferred embodiment the port 161 is fluidly connected to a filterwhich acts to trap any substance driven through the respective nosepieceunit 127, 129.

In this embodiment the clearance hole 163 is configured to be a sealingfit with a driving rod 181 of a respective drive unit 175, 177 of theactuation unit 123, but in other embodiments need not be a sealing fit,as there is no requirement for a sealing fit. In an alternativeembodiment the rear wall of each cylinder 157 can comprise a resilientmaterial which is deflected by the drive rod 181 of the respective driveunit 175, 177 of the actuation unit 123 in driving the rear piston 155of the respective substance supply unit 143 and the piston 159 of therespective gas supply unit 145.

The rear section 157 a of the cylinder 157 has a greater radialdimension than the piston 159 such that, when the piston 159 is in thenon-actuated position, an annular channel is defined about the piston159 in fluid communication with the port 161, whereby a gas flow driveninto the respective nosepiece unit 127, 129 from the other nosepieceunit 127, 129 is vented to atmosphere through the port 161. In thisembodiment the first and second delivery units 139, 141 are actuated insuccession such that the piston 159 of one of the delivery units 139,141 is in the non-actuated position during actuation of the other of thedelivery units 139, 141, thereby providing a flow path through therespective one of the nosepiece units 127, 129.

The intermediate section 157 b of the cylinder 157 has the same radialdimension as the piston 159 such that the piston 159 is a sealing fittherein, whereby a gas flow is driven through the respective deliverychannel 137 during displacement of the piston 159 thereover. In thisembodiment the volume of the gas flow is determined by the length of theintermediate section 157 b of the cylinder 157.

The forward section 157 c of the cylinder 157 has a greater radialdimension than the piston 159 such that, when the piston 159 is in theactuated position, an annular channel is defined about the piston 159 influid communication with the port 161, whereby a gas flow driven intothe respective nosepiece unit 127, 129 from the other nosepiece unit127, 129 is vented to atmosphere through the port 161. In thisembodiment, where the first and second delivery units 139, 141 areactuated in succession, the piston 159 of the other of the deliveryunits 139, 141, that is, the delivery unit 139, 141 which is firstactuated, is in the actuated position during actuation of the other ofthe delivery units 139, 141, thereby providing a flow path through theother nosepiece unit 127, 129.

The piston 159 comprises an annular element 165 and a connecting rod 166which is coupled to the rear piston 155 of the respective substancesupply unit 143. The annular element 165 includes a stepped peripheraledge 167, the peripheral edge 167 including a first, forward section 167a having the same radial dimension as the intermediate section 157 b ofthe cylinder 157 such as to be a sealing fit therewith, and a second,rear section 167 b having a smaller radial dimension than the forwardsection 167 a such as to provide an annular flow path about theperipheral edge 167 when the piston 159 is in the actuated position.

In this embodiment the annular element 165 is configured to sealinglyengage the rear end of the respective cylinder 157, and thereby closethe respective clearance hole 163, when the piston 159 is in thenon-actuated position.

The interface unit 121 further comprises a mouthpiece unit 169 intowhich the subject exhales to actuate the actuation unit 123. In thisembodiment the mouthpiece unit 169 comprises a mouthpiece 171, hereconfigured to be gripped in the lips of the subject, and a flexibleelement 173, here a resilient membrane, which is disposed across therear end of the mouthpiece 171 such as to be acted upon by theexhalation breath of the subject and be deflected thereby. As will bedescribed in more detail hereinbelow, the actuation unit 123 includes atrigger mechanism 191 which is actuated by a predetermined deflection ofthe flexible element 173, which deflection corresponds to theestablishment of a predetermined pressure in the oral cavity of thesubject sufficient for closure of the oropharyngeal velum. FIG. 12(b)illustrates the state where a subject is exhaling into the mouthpiece171 of the mouthpiece unit 169 such as to cause deflection of theflexible element 173, but prior to the actuation of the delivery units139, 141.

The actuation unit 123 comprises a housing 174 to which an interfaceunit 121 is attachable for the treatment of a subject.

The actuation unit 123 further comprises first and second drive units175, 177 which are actuatable to actuate respective ones of the deliveryunits 139, 141 in response to exhalation by the subject. FIGS. 12(b) and(e) illustrate the first and second drive units 175, 177 in respectiveones of the loaded, but non-actuated and actuated configurations.

The drive units 175, 177 each comprise a drive member 179 which ismovable between a first, rest position in which the respective deliveryunit 139, 141 is in the non-actuated position and a second, actuatedposition in which the piston 159 of the respective gas supply unit 145and the rear piston 155 of the respective substance supply unit 143 areadvanced to the actuated position. In this embodiment the drive member179 includes a drive rod 181 which extends through the respectiveclearance aperture 163 in the main body 125.

The drive units 175, 177 each further comprise a load biasing element183, in this embodiment a resilient element, particularly a compressionspring, for biasing the respective drive member 179 in an actuatingdirection when in the rest position.

The actuation unit 123 further comprises a loading assembly 185 forcommonly loading the load biasing element 183 of each of the drive units175, 177 such as to bias the drive member 179 of each of the drive units175, 177 when in the rest position with an actuation force.

The loading assembly 185 comprises a loading block 187 which is commonlycoupled to the load biasing elements 183 of the drive units 175, 177,and a loading member 189, in this embodiment a lever, for moving theloading block 187 between a first, inoperative position in which theload biasing elements 183 are not loaded thereby, and a second,operative position in which the load biasing elements 183, whenrestrained, load the respective drive members 179 with the actuationforce.

The actuation unit 123 further comprises a trigger mechanism 191 whichis configured normally to lock the drive members 179 of the drive units175, 177 in the rest position and release the same in succession onexhalation by the subject through the mouthpiece 171, which drivemembers 179, as loaded by the respective load biasing elements 183, oncereleased act commonly to actuate the respective delivery units 139, 141.

In this embodiment the trigger mechanism 191 is configured to causesuccessive actuation of the drive units 175, 177 on generation of apredetermined pressure within the mouthpiece 171. FIGS. 12(c) and 12(d)illustrate the actuation of respective ones of the first and seconddrive units 175, 177.

In another embodiment the trigger mechanism 191 could be configured tocause the successive actuation of the drive units 175, 177 on generationof a predetermined flow rate through the mouthpiece 171.

The trigger mechanism 191 comprises a release element 193, here aslideable element including a lateral projection 195, which is disposedsuch as to be engaged by the flexible element 173 of the mouthpiece unit169 on deflection of the same by the subject exhaling into themouthpiece 171 at a predetermined pressure and moved from a first,locking position, as illustrated in FIG. 12(a), in which the releaseelement 193 acts to lock the trigger mechanism 191 to prevent actuationof the same and a second, release position, as illustrated in FIG.12(b), in which the trigger mechanism 191 is released to enablesuccessive actuation of the delivery units 139, 141.

In this embodiment the trigger mechanism 191 further comprises a biasingelement 194, in this embodiment a resilient element, particularly acompression spring, for biasing the release element 193 to the lockingposition, so as to apply a predetermined actuation force to the flexibleelement 173 in the mouthpiece 171 of the mouthpiece unit 169 and therebyrequire a predetermined actuation pressure to be developed in themouthpiece 171 prior to actuation of the trigger mechanism 191.

The trigger mechanism 191 further comprises a linkage assembly 197 whichincludes first and second link elements 199, 201, which, when in alocking configuration, act to support the drive member 179 of the firstdrive unit 175 in the rest position and prevent movement thereof whenloaded by the respective load biasing element 183. The linkage assembly197 is maintained in the locking configuration by the lateral projection195 of the release element 193 when in the locking position. One of thelink elements 199 is pivotally coupled at one end to the drive member179 of the first drive unit 175, and the other of the link elements 201is pivotally coupled at one end to the other end of the first linkelement 199 and at the other end to the housing 174.

The trigger mechanism 191 further comprises a biasing element 203, inthis embodiment a resilient element, particularly a compression spring,for biasing the linkage assembly 197 from the locking configuration,such that, on movement of the release element 193 from the lockingposition to the release position through deflection of the flexibleelement 173 in the mouthpiece 171 of the mouthpiece unit 169, asillustrated in FIGS. 12(a) and (b), the biasing element 203 acts tocollapse the linkage assembly 197, with which collapse the drive member179 of the first drive unit 175 is driven by the load biasing element183 thereof to actuate the first delivery unit 139, as illustrated inFIG. 12(c).

The trigger mechanism 191 farther comprises a lever assembly 205, which,when in a locking position, as illustrated in FIG. 12(b), acts tosupport the drive member 179 of the second drive unit 177 in the restposition and prevent movement thereof when loaded by the respective loadbiasing element 183.

In this embodiment the lever assembly 205 comprises an L-shaped lever206 which includes first and second arms 207, 209.

One arm 207 of the lever 206 is mounted at one end thereof about a pivot211 such as to be rotatable between a locking position, as illustratedin FIG. 12(b), in which the distal end of the one arm 207 engages thedrive member 179 of the second drive unit 177 such as to preventmovement thereof when loaded by the respective load biasing element 183,and a release position, as illustrated in FIG. 12(c), in which the lever206 is rotated such as to release the drive member 179 of the seconddrive unit 177 from the locking position and thereby actuate the seconddelivery unit 141, as illustrated in FIG. 12(d).

In this embodiment the lever assembly 205 includes a stop 213 which actsas an abutment against which the lever 206 is supported in the lockingposition, and a biasing element 215, here a compression spring, forbiasing the lever 206 to the locking position.

The other arm 209 of the lever 206 is configured to be engaged by thelinkage assembly 197 when the drive member 183 of the first drive unit175 approaches the actuated position, as illustrated in FIG. 12(c),which engagement acts to rotate the lever 206 to move the lever 206 tothe release position, in which position the load biasing element 183 ofthe second drive unit 177 acts to drive the drive member 179 thereof tothe actuated position and thereby actuate the second delivery unit 141.

Operation of the delivery device is illustrated in FIGS. 12(a) to (e),where FIG. 12(a) illustrates the priming of the delivery device and thefitting of the nosepiece units 127, 129 to the respective nostrils of asubject, and, following exhalation by the subject into the mouthpiece171 of the mouthpiece unit 169, FIG. 12(b) illustrates the state where asufficient pressure has been developed in the mouthpiece 171 as to causedeflection of the flexible element 173 in the mouthpiece 171 and allowactuation of the trigger mechanism 191, FIGS. 12(c) and (d) illustratethe successive actuation of the first and second delivery units 139,141, and FIG. 12(e) illustrates the state subsequent to delivery.

Finally, it will be understood that the present invention has beendescribed in its preferred embodiments and can be modified in manydifferent ways without departing from the scope of the invention asdefined by the appended claims.

For example, the delivery device of the first described embodiment couldbe modified such that the entraining gas flow is supplied by theactuation unit 23. In this modification, the interface unit 21 ismodified to omit the gas supply units 45, with the pistons 59 of theinterface unit 21 in this embodiment being modified to omit the annularelements 65 thereof, and the actuation unit 23 is modified to include agas supply unit for selectively supplying a gas flow to the deliverychannels 37 of the nosepiece units 27, 29 through the ports 61, the gassupply unit being configured to vent to atmosphere the other of theports 61 than to which the gas flow is being supplied. Thisconfiguration enables a high flow rate to be developed, where desired.In a preferred embodiment the gas supply unit includes a one-way checkvalve to prevent back-flow thereinto of gas which has been exposed tothe nasal airway of a subject.

In another modification, the interface units 21, 121 of the describedembodiments can be configured such as to allow the interface units 21,121 to be broken along a line between the nosepiece units 27, 29, 127,129, and thereby allow for the separation of the delivery units 39, 41,139, 141. In this way, the delivery units 39, 41, 139, 141 can be usedto deliver single doses of substance to subjects where an actuation unit23, 123 is not available.

In a further modification, the interface units 21, 121 can be modifiedto omit the rear wall of the main body 25, 125 adjacent the gas supplyunits 45, 145 such as to allow for the manual actuation of the deliveryunits 39, 41, 139, 141 by depression of the respective piston 59, 159.Such manual actuation of the delivery units 39, 41, 139, 141 would alsobe possible where the rear wall of the main body 25, 125 adjacent thegas supply units 45, 145 is a flexible element, typically a resilientelement, or where the pistons 59, 159 include an actuation rod whichextends through the respective clearance aperture 63, 163, with manualactuation of the delivery units 39, 41, 139, 141 being achieved bydepression of the respective actuation rod. This modification would alsoextend to delivery units 39, 41, 139, 141 which include no piston 59,159.

In a yet further modification, the interface units 21, 121 can includeonly one nosepiece unit 27, 29, 127, 129 and associated delivery unit39, 41, 139, 141. In one embodiment the mouthpiece 71, 171 can befluidly connected to the delivery channel 37, 137 of the one nosepieceunit 27, 29, 127, 129, with the exhalation breath of a subject providingthe entraining gas flow. Such an embodiment provides for both automatedactuation by an actuation unit 23, 123 where deflection of the flexibleelement 73, 173 of the mouthpiece unit 69, 169 acts to actuate theactuation unit 23, 123, and manual actuation where the subjectsimultaneously exhales and manual actuates a delivery unit 39, 41, 139,141.

In the described embodiments the mouthpieces 71, 171 are configured tobe gripped in the lips of a subject. In alternative embodiments themouthpieces 71, 171 could be configured to be gripped by the teeth of asubject and sealed by the lips of the subject. In preferred embodimentsthe mouthpieces 71, 171 could be specifically configured to have one orboth of a shape or geometry which allows the delivery devices to begripped repeatedly in the same position, thereby providing for therespective nosepiece units 27, 29, 127, 129 to be reliably inserted inthe same position in the nasal cavity.

In preferred embodiments the delivery units are configured to deliversubstance through one nostril of a subject at such a pressure as to flowaround the posterior margin of the nasal septum and out of the othernostril of the subject, thereby achieving bi-directional deliverythrough the nasal cavities as disclosed in WO-A-00/51672. In alternativeembodiments the delivery units could be configured to deliver substanceat a reduced pressure which is not sufficient to achieve bi-directionaldelivery through the nasal cavities. Such embodiments are stilladvantageous as compared to known delivery devices in providing forvelum closure.

1. (canceled)
 2. An interface unit comprising: a nosepiece for fittingto a first nostril of a subject, the nosepiece comprising a nozzle fordelivery of a substance to the subject; and a substance supply unit fromwhich the substance is delivered to the nozzle; wherein the interfaceunit is configured to be clipped to an actuation unit.
 3. The interfaceunit of claim 2, wherein the interface unit is replaceable.
 4. Theinterface unit of claim 2, wherein the substance is a powder.
 5. Theinterface unit of claim 2, wherein the substance is a liquid.
 6. Theinterface unit of claim 2, wherein the nosepiece comprises a cuff memberfor positioning the nosepiece within the first nostril of the subject.7. The interface unit of claim 2, wherein the nozzle is configured togenerate an aerosol spray.
 8. An interface unit comprising: a nosepiecefor fitting to a first nostril of a subject, the nosepiece comprising anozzle for delivery of a substance to the subject; and a substancesupply unit from which the substance is delivered to the nozzle; whereinthe interface unit is configured to be slidingly attached to anactuation unit.
 9. The interface unit of claim 8, wherein the interfaceunit is replaceable.
 10. The interface unit of claim 8, wherein thesubstance is a powder.
 11. The interface unit of claim 8, wherein thesubstance is a liquid.
 12. The interface unit of claim 8, wherein thenosepiece comprises a cuff member for positioning the nosepiece withinthe first nostril of the subject.
 13. The interface unit of claim 8,wherein the nozzle is configured to generate an aerosol spray.
 14. Aninterface unit comprising: a nosepiece for fitting to a first nostril ofa subject, the nosepiece comprising a nozzle for delivery of a substanceto the subject; and a substance supply unit from which the substance isdelivered to the nozzle, the substance supply unit containing a metereddose of the substance.
 15. The interface unit of claim 14, wherein theinterface unit is replaceable.
 16. The interface unit of claim 14,wherein the interface unit is configured to be slidingly attached to anactuation unit.
 17. The interface unit of claim 14, wherein theinterface unit is configured to be clipped to an actuation unit.
 18. Theinterface unit of claim 14, wherein the substance is a powder.
 19. Theinterface unit of claim 14, wherein the substance is a liquid.
 20. Theinterface unit of claim 14, wherein the nosepiece comprises a cuffmember for positioning the nosepiece within the first nostril of thesubject.
 21. The interface unit of claim 14, wherein the nozzle isconfigured to generate an aerosol spray.